Hazardous substance assessment - Diethylene Glycol Monomethyl Ether

Identification

Chemical name:

Diethylene glycol monomethyl ether (DEGME)

CAS #:

111-77-3

Chemical composition:

C₅H₁₂O₃

Synonyms:

Ethanol, 2-(2-methoxyethoxy)-; 2-(2-Methoxyethoxy)ethanol; Methyl carbitol; Methoxydiglycol; DEGME; Dowanol 16; EGME-di; (French name) Éther de diéthylèneglycol et de monométhyle.

UN #:

Not available

Pictogram(s):

Figure 1 - Text description

The symbol within the pictogram is a black silhouette of a person's head and chest with a white star shape spreading out from the center of the chest. This symbol indicates that hazardous products with this pictogram can cause certain health effects for example:

• carcinogenicity,
• specific target organ effects following single or repeated exposure, or
• reproductive toxicity.

WHMIS classification

Health hazards:

Reproductive toxicity: Category 2

Physical hazards:

Flammable Liquids: Category 4

Health hazards

Acute Toxicity (Oral):

Does not meet criteria

LD­₅₀: 7,128 mg/kg (rat) ^Footnote 1.

The available data do not meet the classification criteria for Acute Toxicity (Oral).

Acute Toxicity (Dermal):

Does not meet criteria

LD₅₀: 9,404 mg/kg (rabbit) ^Footnote 1.

The available data do not meet the classification criteria for Acute Toxicity (Dermal).

Acute Toxicity (Inhalation – Gas):

No data available

Acute Toxicity (Inhalation – Vapour):

Does not meet criteria

LC₅₀: >1.47 mg/L, 4 h (0/10 deaths – saturated vapour concentration) (based on study summary ^Footnote 2).

The available data do not meet the classification criteria for Acute Toxicity (Inhalation - Vapour).

Acute Toxicity (Inhalation – Dust and Mist):

No data available

Skin Corrosion / Irritation:

Does not meet criteria

In a skin irritation study performed similar to the Organization for Economic Co-operation and Development Test Guideline (OECD TG) 404, 6 rabbits (3/sex) received 0.5 mL of the test substance on an intact skin for 4 h under occlusive conditions (based on study summary ^Footnote 2). No irritation was observed at any time point up to 3 days. The average scores (24, 48, and 72 h) for erythema and edema were 0. In a Draize study, application of DEGME at a dose as high as 20 g/kg to rabbit and guinea pigs' skin resulted in slight skin irritation ^Footnote 1.

The available data do not meet the classification criteria for Skin Corrosion / Irritation.

Serious Eye Damage / Eye Irritation:

Does not meet criteria

In an eye irritation study performed in accordance with OECD TG 405, DEGME tested negative for eye irritation when 0.1 mL was applied to 6 rabbit eyes (based on study summary ^Footnote 2). The average score (24-48-72 h) was 0.1/3 for conjuctivae; 0.1/4 for chemosis and 0 for cornea and iris. One drop of undiluted DEGME in to rabbit eyes for 6 consecutive days caused very slight irritation with no corneal effects ^Footnote 3. A repeat application of undiluted test material into rabbit eyes daily for 5 days, 10 times in 2 weeks, failed to cause more than a mild irritation in another eye irritation study, no further details given ^Footnote 4.

The available data do not meet the classification criteria for Serious Eye Damage / Eye Irritation.

Respiratory Sensitization:

No data available

Skin Sensitization:

Does not meet criteria

Human data: Results were negative in a human patch test when tested at 20% in petrolatum ^Footnote 5.

Animal data: In an OECD TG 406 compliant guinea pig maximization study, DEGME showed no signs of skin sensitization (based on study summary ^Footnote 2). Intradermal induction was performed using 5% DEGME in isotonic saline and dermal induction and challenge exposures used undiluted material.

The available data do not meet the classification criteria for Skin Sensitization.

Germ Cell Mutagenicity:

Does not meet criteria

No in vivo data are available. Results were negative in the Ames test in bacterial cells with and without metabolic activation ^Footnote 6. Results were also negative in a chromosomal aberration assay in Chinese Hamster Ovary cells, with and without metabolic activation ^Footnote 5.

The available data do not meet the classification criteria for Germ Cell Mutagenicity.

Carcinogenicity:

No data available

DEGME has not been reviewed by the International Agency for Research on Cancer (IARC), the National Toxicology Program (NTP), or the American Conference of Governmental Industrial Hygienists (ACGIH).

Reproductive Toxicity:

Category 2

In a developmental toxicity study performed in accordance with OECD TG 414, pregnant rats were administered with DEGME orally in doses of 0, 200, 600, and 1,800 mg/kg during GD7 -17 of gestation ^Footnote 7. Fetotoxicity without maternal toxicity was observed at 600 mg/kg and teratogenicity with slight maternal toxicity which manifested in the form of small but significant weight reduction, particularly thymus, occurred at 1,800 mg/kg. Fetal body weights in both sexes were decreased in a dose-dependent manner with significance at 600 and 1,800 mg/kg. External malformations were observed in 14.1% of the fetuses at 1,800 mg/kg and visceral malformations were observed at both 600 mg/kg (2.4%) and 1,800 mg/kg (28.0%). Ossification was considerably affected at doses >600 mg/kg. The high dose animals showed evidence of developmental toxicity, with a significant reduction in the number of live pups and an increase in gestation period by about 2 days. The body weight gain of pups during the first 21 days was slightly decreased at 600 mg/kg. In a screening study, DEGME, when administered orally to mice at 4,000 mg/kg (representing 10% maternal mortality - LD10) on days 7-14 of gestation, resulted in a significant reduction in viable litters, number of live pups /litter, and percent pup post-natal survival (p<0.05) (16% viable litters vs 97% for controls) ^Footnote 8. This dose also produced maternal toxicity in the form of reduced weight gain and adverse hematological changes.

In studies with rabbits, DEGME was administered topically to pregnant rabbits at doses of 0, 50, 250, and 750 mg/kg on days 6-18 of gestation ^Footnote 9. Maternal toxicity in terms of reduced weight gain and hematological changes was observed in the high dose group (750 mg/kg) only. There were no statistically significant differences in reproductive parameters compared to controls, although the incidence of resorptions was slightly higher in this dose group. Fetotoxicity in the form of lower fetal body weights, fetal malformation and delayed ossification of the skull and cervical spurs was seen in the 250 and 750 mg/day dose groups. No evidence of teratogenic effects was found at levels up to 750 mg/kg. Similar effects were observed in another study when pregnant rabbits were administered with DEGME dermally at 1,000 mg/kg/day on days 6-18 of organogenesis ^Footnote 10.

The available data meet the classification criteria for Reproductive Toxicity – Category 2 [HPR 8.7.1(1)].

Specific Target Organ Toxicity – Single Exposure:

Does not meet criteria

Oral Route of Exposure: No human data are available. Based on high oral LD₅₀ value in rats (7,128 mg/kg) ^Footnote 1, DEGME does not meet classification criteria.

Dermal Route of Exposure: No human data are available. Based on the high dermal LD₅₀ value in the rabbit (9,404 mg/kg) ^Footnote 1, DEGME does not meet classification criteria.

Inhalation Route of Exposure: No human data are available. In an animal acute toxicity study performed according to OECD TG 403, rats were exposed to a single dose of the saturated vapour concentration of DEGME for a period of 6 h (based on study summary ^Footnote 2). No signs of toxicity were observed.

The available data do not meet the classification criteria for Specific Target Organ Toxicity – Single Exposure.

Specific Target Organ Toxicity – Repeated Exposure:

Does not meet criteria

Oral Route of Exposure: No human data are available. In animal studies, administration of 1,000 mg/kg DEGME in rats for 20 days reduced thymus weight to about 65% of control; however, no effect on testes or thymus weight was observed at a lower dose of 500 mg/kg ^Footnote 11. Decrease in liver weights were reported at 2,000 mg/kg when DEGME was administered for 20 days in rats ^Footnote 12. Similar results were reported in another well conducted sub-acute study where rats (10/group) were administered daily with 900, 1,800, and 3,600 mg/kg DEGME, 5 days a week for 6 weeks. A number of adverse effects were seen in the high dose group, the most notable being adverse testicular changes. At mid dose, inconsistent increases or decreases were reported in either relative or absolute organ weights. No treatment related changes were seen in the low dose group ^Footnote 1. Since adverse effects were reported at high doses only, results of these studies do not meet criteria for classification.

Dermal Route of Exposure: No human data are available. In a 13 weeks study, guinea pigs were exposed to 40, 200, and 1,000 mg/kg of DEGME, 6 h/day, 5 days/week ^Footnote 13. Exposed animals showed decreased splenic weights in the 200 and 1,000 mg/kg dose groups only. Isolated but significant changes were also seen in the high dose group's clinical chemistry (LDH level) and haematology (MCHC level). The effects occurred at doses that exceed the concentration value range and hence do not meet classification criteria.

Inhalation Route of Exposure: No human data are available. In an animal study, male and female rats were exposed to 0, 30, 100, or 216 ppm DEGME vapors (0, 0.15, 0.49 or 1.06 mg/L) 6 h per day, 5 days per week, for 13 weeks ^Footnote 14. The high concentration tested is the maximum practically attainable concentration. No significant clinical effects were noted.

The available data do not meet the classification criteria for Specific Target Organ Toxicity – Repeated Exposure.

Aspiration Toxicity:

No data available

Biohazardous Infectious Materials:

Not applicable

DEGME is not a microorganism, protein, or nucleic acid.

Physical hazards

Explosives:

Not Evaluated*

* Explosives are excluded from the Hazardous Products Act and Regulations. Explosives are regulated under the Explosives Act. For more information, visit Natural Resources Canada.

Flammable Gases:

Does not meet criteria

DEGME presents no significant physicochemical hazard with respect to flammability. Based on information available in secondary sources, the flammability of the substance ranges from 1.4% (Lower Explosion Limit) to 23% (Upper Explosion Limit) (based on study summaries ^Footnote 2). This information combined with the data on the flash point/low vapour pressure led to the conclusion that this substance does not meet criteria for this category.

The available data do not meet the classification criteria for Flammable Gases.

Flammable Aerosols:

No data available

In order for a substance to produce flammable aerosols, it has to be packaged in an aerosol can and no information is available in this regard for this substance.

No data are available to determine whether DEGME meets the classification criteria for Flammable Aerosols.

Oxidizing Gases:

Not applicable

DEGME is not a gas. The classification criteria for Oxidizing Gases do not apply to this substance.

Gases Under Pressure:

Not applicable

DEGME is not a gas. The classification criteria for Gases Under Pressure do not apply to this substance.

Flammable Liquids:

Category 4

A number of values are available for the flashpoint of DEGME. All of these values are derived from a secondary source with no original source of data. The flash point is reported to be between 91°C and 96°C (closed cup) and 83°C (open cup) (based on study summary ^Footnote 2). Considering that closed cup measurements include the upper limit for classification (93°C), DEGME meets the classification criteria for Flammable Liquids – Category 4

The available data meet the classification criteria for Flammable Liquids – Category 4 [HPR 7.6.1(2)].

Flammable Solids:

Not applicable

DEGME is not a solid. The classification criteria for Flammable Solids do not apply to this substance.

Self-Reactive Substances and Mixtures:

Does not meet criteria

According to secondary sources, a number of auto-ignition temperatures are available for DEGME, ranging from 215°C to 250°C (based on study summaries ^Footnote 2). Self-Reactive Substances and Mixtures must have a self-accelerating decomposition temperature (SADT) of ≤75°C to meet the minimum classification in this category.

The available data do not meet the classification criteria for Self-Reactive Substances and Mixtures.

Pyrophoric Liquids:

Does not meet criteria

The substance DEGME does not ignite on contact with air (based on study summary ^Footnote 2).

The available data do not meet the classification criteria for Pyrophoric Liquids.

Pyrophoric Solids:

Not applicable

DEGME is not a solid. The classification criteria for Pyrophoric Solids do not apply to this substance.

Self-Heating Substances and Mixtures:

Does not meet criteria

DEGME has an auto-ignition temperature between 215 °C and 250 °C (based on study summary ^Footnote 2), which is above the spontaneous ignition temperature for classification.

The available data do not meet the classification criteria for Self-Heating Substances and Mixtures.

Substances and Mixtures which, in Contact with Water, Emit Flammable Gasses:

Not applicable

DGME has a chemical structure that does not contain metals or metalloids and is, therefore, excluded from classification [HPR 7.12.1(1)]. DEGME does not ignite on contact with air (based on study summary ^Footnote 2).

Oxidizing Liquids:

Not applicable

Section 7.13.1(1)(b) of the HPR excludes from classification any organic liquid that contains oxygen, fluorine or chlorine if those elements are chemically bonded only to carbon and hydrogen. Substance DEGME contains oxygen that is chemically bonded to carbon and hydrogen.

Oxidizing Solids:

Not applicable

DEGME is not a solid. The classification criteria for Oxidizing Solids do not apply to this substance.

Organic Peroxides:

Not applicable

DEGME is not an organic peroxide. The classification criteria for Organic Peroxides do not apply to this substance.

Corrosive to Metals:

Does not meet criteria

In spite of extensive use in products exposed to metal [such as products for cleaning and caring for automobiles (auto shampoo, polish/wax, undercarriage treatment, brake grease etc.)], there is no evidence that DEGME is corrosive to metal.

The available data do not meet the classification criteria for Corrosive to Metals.

Combustible Dusts:

Not applicable

DEGME is not a solid. The classification criteria for Combustible Dusts do not apply to this substance.

Simple Asphyxiants:

Not applicable

Substance DEGME is not a gas. The classification criteria for Simple Asphyxiants do not apply to this substance.

Pyrophoric Gases:

Not applicable

DEGME is not a gas. The classification criteria for Pyrophoric Gases do not apply to this substance.

Regulatory and other information

Regulatory information:

Hazardous substance assessments are prepared by Health Canada as educational and information resources. Under the HPA, suppliers of hazardous products must, upon the sale or importation of a hazardous product, provide a safety data sheet and label that meet the requirements set out in the HPR.

Other information:

The information and classifications contained in these hazardous substance assessments are based on publicly available sources, such as peer-reviewed literature or reports by international bodies. New information, including proprietary information, could have an impact on the classification of substances or hazardous products containing them. It is the responsibility of the supplier to ensure the accuracy, sufficiency, and reliability of their hazardous product classifications.

Last updated:

2020

Prepared by:

Workplace Hazardous Materials Bureau, Health Canada